The risk of vitamin B12 deficiency increases with age. Furthermore, detection of this serious condition is problematic in the elderly, who may present with neither a serum vitamin B12 concentration <148 pmol/L nor hematologic abnormality. The prevalence of these atypical presentations, which may carry a heightened risk of neurological damage, is likely to increase in the post-folate-fortification era due to the masking of anemia by high folate status. Better screening methods are needed to bring atypical cases to light and prevent unnecessary treatment. New vitamin B12 status indicators, including the metabolites homocysteine and methylmalonic acid, have been proposed, but tests of their utility have been performed mainly in those later confirmed to be deficient. Whether positive results from these new tests might often falsely indicate deficiency is currently unknown, nor has their ability to detect classic and atypical cases occurring in the general population been tested. This application proposes to use metabolite concentrations and other vitamin B12 status indicators measured in the third National Health and Nutrition Examination Survey to evaluate the usefulness of two proposed new strategies for assessing vitamin B12 status; namely, using elevated serum concentrations of total homocysteine and methylmalonic acid rather than low serum vitamin B12 levels to indicate deficiency, and adopting a higher serum vitamin B12 cut-off point. The significance of this research lies in its potential to improve the detection of vitamin B12 deficiency in the elderly and facilitate early intervention and avoidance of such serious consequences as demyelinization, while at the same time preventing unnecessary testing and treatment. The first aim of this project is to compare younger and older Americans relative to typical and atypical presentations of low serum vitamin B12 status. The second aim is to evaluate the usefulness of elevated serum levels of the metabolites homocysteine and methylmalonic acid for detecting typical and atypical cases of low serum vitamin B12 status. The third aim is to evaluate the usefulness of a serum vitamin B12 cut-off point of 258 pmol/L, either as the sole indicator of vitamin B12 deficiency in the elderly, or in conjunction with anemia or an elevated metabolite level. [unreadable] [unreadable]